Gelatin is a commonly used natural polymer which is derived from collagen. The isoelectric point of gelatin can be modified
during the fabrication process to yield either a negatively charged acidic gelatin, or a positively charged basic gelatin at
physiological pH. This theoretically allows electrostatic interactions to take place between a charged biomolecule and gelatin of
the opposite charge, forming polyion complexes. Various forms of gelatin carrier matrices can be fabricated for controlledrelease
studies, and characterization studies have been performed which show that gelatin carriers are able to sorb charged
biomolecules such as proteins and plasmid DNA through polyion complexation. The crosslinking density of gelatin hydrogels
has been shown to affect their degradation rate in vivo, and the rate of biomolecule release from gelatin carriers has been shown
to have a similar profile, suggesting that complexed gelatin/biomolecule fragments are released by enzymatic degradation of the
carrier in vivo. This review will emphasize how biomolecules released from gelatin controlled-release systems are able to retain
their biological activity, allowing for their use in tissue engineering, therapeutic angiogenesis, gene therapy, and drug delivery
applications.